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Sex differences in neonatal and young adult rat lower urinary tract function caused by bladder reduction
China Chien1, Huiyi Harriet Chang2, Hsi-Yang Wu1
1Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
Insights
Neonatal bladder reduction in rats caused temporary external urethral sphincter (EUS) dysfunction, particularly in females. Early EUS impairment may lead to long-term bladder issues, especially in females, highlighting the need for timely intervention.
Area of Science:
- Urology
- Developmental Biology
- Animal Models
Background:
- Pediatric urinary incontinence is a potential precursor to adult incontinence.
- Existing animal models often mimic overactive bladder rather than dysfunctional voiding.
- The bladder reduction (BR) model was utilized to investigate early external urethral sphincter (EUS) dysfunction effects on lower urinary tract maturation.
Purpose of the Study:
- To assess long-term bladder and EUS functional changes in young adult rats following neonatal BR.
- To investigate the impact of early EUS dysfunction on lower urinary tract development in a rat model.
Main Methods:
- Neonatal rats (n=98) underwent either BR or sham surgery at 1 week of age.
- Cystometry was performed at 3, 6, and 9 weeks.
- Administration of serotonergic agents (8-OH-DPAT and WAY 100,635) to evaluate EUS and bladder responses.
Main Results:
- Neonatal BR induced temporary EUS emptying impairment (reduced burst amplitude) in 3-week-old females and males.
- Female rats showed increased pressure and volume thresholds for voiding, indicating long-term bladder dysfunction.
- EUS function spontaneously recovered by 6-9 weeks, and serotonergic agent responses were similar between BR and sham groups.
Conclusions:
- Neonatal BR temporarily mimics dysfunctional voiding by impairing EUS emptying.
- While EUS function recovers, persistent increases in voiding volume threshold in female rats suggest a risk for long-term bladder dysfunction.
- Timely treatment of EUS dysfunction is crucial to mitigate the risk of enduring lower urinary tract issues.
Introduction:
Pediatric urinary incontinence has been proposed as a cause for adult urinary incontinence, yet animal models mimic the findings of overactive bladder more closely than dysfunctional voiding. We used the bladder reduction (BR) model to study the effects of early external urethral sphincter (EUS) dysfunction on the maturation of lower urinary tract function in neonatal and young adult rats of both sexes.
Objective:
To determine long-term alterations in bladder and EUS function in young adult rats caused by neonatal BR.
Materials And Methods:
46 Sprague-Dawley rats underwent BR and 52 underwent sham surgery at 1 week of age. At 3, 6, and 9 weeks of life, cystometry was carried out, 8-OH-DPAT (serotonergic receptor agonist) and WAY 100,635 (serotonergic receptor antagonist) were administered intravenously. Pressure threshold (PT), volume threshold (VT), storage tonic AUC, contraction area under the curve (AUC), EUS burst amplitude and burst duration were measured at baseline and after administration of serotonergic agents.
Results:
PT increased in 3-week BR females compared with shams (31.1 vs. 22.7 cm H2O, p < 0.01), in conjunction with less efficient EUS emptying, as burst amplitude was suppressed (BR 0.04 vs. sham 0.07 mV, p < 0.05). VT subsequently increased in 9-week BR females compared with shams (0.81 vs. 0.36 mL, p < 0.05). Although 3-week BR males also experienced suppressed burst amplitude (BR 0.17 vs. sham 0.28 mV, p < 0.05), they showed no difference in PT at 3 weeks or VT at 9 weeks compared with sham males. The burst amplitude returned to normal in 6- and 9-week BR animals of both sexes, confirming a spontaneous recovery of EUS function over time. The thresholds for voiding in male rats are not as sensitive to early changes in EUS function compared with female rats. The response to serotonergic agents was identical between BR and sham animals. In the female animals, 8-OH-DPAT increased storage tonic AUC and burst duration, whereas in male animals, 8-OH-DPAT increased contraction AUC, burst amplitude, and burst duration. WAY 100,635 reversed the enhancements of EUS function caused by 8-OH-DPAT.
Conclusions:
BR caused a temporary impairment of EUS emptying at 3 weeks of life, similar to dysfunctional voiding, while serotonergic agonists remained effective at enhancing EUS emptying in BR animals. Although EUS emptying spontaneously improved, the increase in VT in female young adult rats suggests that timely treatment of EUS dysfunction is required to decrease the risk of long-term bladder dysfunction.
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